GDF15 serves as a coactivator to enhance KISS-1 gene transcription through interacting with Sp1.
Zhou. Bo B; Huang. Wen-He WH; Chen. Shaoying S; Chen. Weibin W; Peng. Pei P; Zhou. Yanchun Y; Gu. Wei W
Key Findings
- GDF15 moves into the nucleus and changes the activity of many genes, including KISS-1.
- In breast cancer cells, GDF15 binds to Sp1 at the KISS-1 promoter, increasing KISS-1 expression.
- Higher KISS-1 levels are linked to reduced cell proliferation and invasiveness.
Practical Outcomes
- The findings are basic cancer‑research insights and do not provide any direct, actionable guidance for health‑optimizing protocols, dosing, or supplementation with kisspeptin‑10. At this stage, the work is not applicable to longevity, metabolic health, or performance goals for the biohacker community.
Summary
The study shows that a protein called GDF15 can go into the cell nucleus and help turn on the KISS-1 gene by teaming up with another protein, Sp1. This boosts KISS-1 levels and slows down the growth of breast cancer cells in the lab.
Abstract
GDF15 has been recently recognized as a tumor-suppressive gene. However, the underlying mechanism by which GDF15 affects breast carcinogenesis is not well understood. Here, we showed that the inhibitory effect of GDF15 on cell proliferation was dependent on the nuclear localization of the protein. Dynamic translocation of GDF15 into the nucleus altered expression of a number of genes, including KISS-1, and resulted in inhibition of cell growth and invasive behavior. Using KISS-1 promoter-driven luciferase reporter and chromatin immunoprecipitation assays, we demonstrated that, in highly malignant breast cancer cells, GDF15 directly interacts with specific protein-1 (Sp1) at the Sp1-binding sites of the KISS-1 promoter, leading to upregulated KISS-1 expression. Our study indicates that nuclear GDF15 could serve as a transcriptional coactivator to mediate the expression of particular genes to reduce cell proliferation.
Study Information
pubmed
2021
2021-02-25T00:00:00.000Z
10.1093/carcin/bgaa103
2
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